Inflammatory cell accumulation in traumatic neuromas of the human lingual nerve.

OBJECTIVE: To quantify the accumulation of inflammatory cells in traumatic neuromas of the human lingual nerve, and to establish any correlation with the patients' reported symptoms of dysaesthesia. DESIGN: Using fluorescence immunohistochemistry, the extent of any chronic inflammatory infiltrate was quantified in human lingual neuroma specimens removed from 24 patients at the time of microsurgical nerve repair. A pan-leucocyte marker (CD45) and a specific macrophage marker (CD68) were used, and comparisons made between neuromas-in-continuity (NICs) and nerve-end neuromas (NENs) in patients with or without symptoms of dysaesthesia. RESULTS: CD68 and CD45 labelling was significantly associated with areas of viable nerve tissue in neuromas and the CD68 labelling was significantly higher in NICs than NENs. CD68 labelling density tended to decrease with increasing time after the initial nerve injury, but this correlation was only significant for labelling associated with viable nerve tissue in NENs. No significant difference was found between the level of CD68 or CD45 labelling in patients with or without symptoms of dysaesthesia. CONCLUSION: This study has demonstrated the presence of inflammatory cells within traumatic neuromas of the human lingual nerve. These cells were found to be closely associated with regions of viable nerve tissue, but there was no correlation with the patients' clinical symptoms.

Ultrastructural characteristics of axons in traumatic neuromas of the human lingual nerve.

AIMS: To determine the ultrastructural characteristics of axons in traumatic neuromas of the human lingual nerve during the surgical removal of lower third molar teeth and to establish whether any characteristics were different between patients with dysesthesia and patients without dysesthesia. METHODS: Transmission electron microscopy was used to determine the ultrastructural morphological characteristics of human lingual nerve neuromas (n = 34) removed at the time of microsurgical nerve repair. From a sample population of myelinated and nonmyelinated fibers within the neuromas, fiber diameter, myelin thickness, g-ratio, and the number of mitochondria per axon were quantified. Comparisons were made with normal control lingual nerve specimens (n = 8) removed at the time of organ donor retrieval. RESULTS: Significant differences in ultrastructural morphology were found between the neuromas and control nerves. The neuromas contained a higher proportion of small (2- to 8-microm diameter) myelinated nerve fibers than controls, and the mean myelinated fiber diameter was significantly lower in neuromas than in controls. Mean myelin sheath thickness was significantly thinner in neuromas (0.6 +/- 0.1 microm) than in controls. However, the g-ratio, which is a measure of the myelination status of the nerve fibers in relation to their diameter, was found to be similar in each group, suggesting a normal process of myelination in the damaged axons. Nonmyelinated axon diameter was also significantly smaller in the neuromas than in the controls, and Schwann cells were found to sheathe more nonmyelinated axons in neuromas than in controls. The ratio of nonmyelinated to myelinated axons was significantly higher in neuromas than in controls. However, no significant differences were found between patients with dysesthesia and those without dysesthesia. CONCLUSION: Damage to the lingual nerve results in marked changes to axon diameter, myelin sheath thickness, and Schwann cell-axon relationships. These ultrastructural changes could contribute to the altered electrophysiological properties of axons trapped within neuromas. However, no significant differences in the ultrastructural characteristics studied were found between specimens from patients with or without symptoms of dysesthesia.

A light microscopical study on the structure of traumatic neuromas of the human lingual nerve.

OBJECTIVE: To determine the morphologic characteristics of traumatic neuromas resulting from damage to the lingual nerve during the surgical removal of lower third molar teeth. STUDY DESIGN: Using light microscopy, we examined hematoxylin and eosin-stained sections of neuromas removed at the time of microsurgical nerve repair in 31 patients. Changes in fascicular pattern were quantified and evidence of inflammation was recorded. Statistical comparisons were made between the sections from patients with and without symptoms of dysesthesia, and with sections of normal lingual nerve obtained from organ donor retrieval patients. RESULTS: The neuromas were found to contain large numbers of small and haphazardly arranged regenerating nerve fascicles within a densely collagenous and fibroblastic stroma. The mean number of fascicles was 31 (+/- SD 28) in normal lingual nerve, but 462 (+/- 366) within traumatic neuromas. Mean fascicle diameter was 44 (+/- 10) microm in neuromas, but 273 (+/- 101) microm in normal nerve. A chronic mononuclear cell inflammatory infiltrate was observed in 42% of neuroma specimens, and histologic signs of inflammation were frequently seen in patients with symptoms of dysesthesia. CONCLUSIONS: Damage to the lingual nerve during third molar removal results in marked changes to the fascicular pattern and sometimes the presence of chronic inflammation in the injured nerve. These changes could contribute to the altered electrophysiological properties of axons trapped within traumatic neuromas, but we found no significant differences between the specimens studied from patients with or without symptoms of dysesthesia.

Close apposition and exposure of non-myelinated axons in traumatic neuromas of the human lingual nerve.

Peripheral nerve injury is sometimes followed by the development of persistent painful sensory disorders, such as dysaesthesia. The aetiology of these disorders is not clear, but abnormal behaviour of damaged axons at the injury site is likely to be involved. In this study, we quantified some ultrastructural characteristics that may be related to the development of abnormal spontaneous activity, sympathetic interactions, and fibre-to-fibre crosstalk. Using electron microscopy, we have determined the frequency and extent of axonal exposure and close apposition among non-myelinated axons from 34 traumatic neuromas of the human lingual nerve. These specimens were removed at the time of microsurgical nerve repair, and the presence or absence of symptoms of dysaesthesia was determined pre-operatively. Comparisons were also made with eight normal control lingual nerve specimens obtained from patients undergoing organ donor retrieval. More non-myelinated axons showed signs of axonal exposure in traumatic neuromas (26%) than in controls (5%), and exposure was higher in nerve-end neuromas (31%) than in neuromas-in-continuity (22%). In addition, the proportion of the non-myelinated axolemma that was exposed was significantly higher in neuromas (32%) than in controls (21%). The frequency of close apposition between neighbouring non-myelinated axons was also higher in neuromas (11%) than in controls (0.35%). The majority of axons showing signs of exposure or close apposition had diameters <1 microm. These ultrastructural changes may account for some of the altered electrophysiological properties of axons within neuromas. However, no significant correlations were found between these ultrastructural characteristics and the patients' reported symptoms of dysaesthesia.

Peripheral mechanisms for the initiation of pain following trigeminal nerve injury.

Injury to a branch of the trigeminal nerve may lead to the development of chronic pain in the affected area. The etiology of this condition is not clear, but there is strong evidence to suggest that spontaneous and mechanically induced neural discharge from the injury site plays a crucial role. In laboratory studies, we have characterized this discharge following injury to the inferior alveolar or lingual nerves and have shown a temporal association with the accumulation of neuropeptides in the damaged axons. Substance P, calcitonin gene-related peptide, and vasoactive intestinal polypeptide were all found to be capable of increasing the discharge when applied systemically, and enkephalin caused a decrease. There were also changes in the expression of specific sodium channels and nitric oxide synthase, both at the injury site and in the trigeminal ganglion. Studies on lingual nerve neuromas taken from patients undergoing nerve repair also revealed accumulation of peptides, as well as inflammatory and structural changes, but the presence of these features did not correlate directly with the reported symptoms. The application of corticosteroids to an experimental injury site decreased the mechanically induced discharge, and the anticonvulsant carbamazepine reduced the spontaneous discharge in some axons. Some of the responses that result from damage to a branch of the trigeminal nerve appear to differ from those that follow damage to other peripheral nerves. These differences will need to be taken into account when developing new therapeutic approaches for the management of injury-induced trigeminal pain.